Abstract
Familial Mediterranean fever (FMF) is a hereditary, autoinflammatory disease characterized by recurrent fever and serositis attacks. The disease onset occurs before 20 years of age in 90% of patients and rarely after the 4th decade. The aim of this study is to screen our FMF patient pool for patients with disease onset after age of 40 and to compare them to patients with early onset with regard to clinical and genetic features. The charts of 2020 patients registered in our FMF center in the years 2008–2017 were screened with regard to age of disease onset. Patients with disease onset after the age of 40 were considered as late-onset group (Group 1). The control group (Group 2) consisted of patients with a disease onset before the age of 20 who were randomly selected from the patient pool with twice the number of probands. Demographic, clinical and genetic data were recorded. Out of 2020 patients, the attacks of FMF had started after the fourth decade in 41 patients (2.02%), (Group 1). The male to female ratio was 1:1.7 in both groups. The delay of diagnosis was 5.6 ± 5.75 years in group 1, 10.7 ± 12.3 years in group 2. The only significant difference with regard to clinical features between two groups was the frequency of fever, which was present in 26 (63.4%) patients in group 1 and 67 (81.7%) in group 2 (p = 0.026). M694V mutation was more prevalent among early-onset group whereas exon 2 variants were more frequent in patients with late onset. The mean colchicine dose in the last 6 months was 1.38 ± 0.64 mg in group 1, and 1.61 ± 0.47 mg in group 2. FMF may start after 40 years of age in approximately 2% of the patients. Lower frequency of fever, lower daily colchicine dose and lower prevalence of exon 10 mutations point out that FMF patients with a disease onset after 40 years of age experience a milder disease compared to those with an onset before the second decade of life.
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04 March 2022
A Correction to this paper has been published: https://doi.org/10.1007/s11739-022-02953-7
References
Lidar M, Livneh A (2007) Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med 65(9):318–324
Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever A survey of 470 cases and review of the literature. Am J Med. 1967;43(2):227–53.
Sönmez HE, Batu ED, Özen S (2016) Familial Mediterranean fever: current perspectives. J Inflamm Res 9:13–20
Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G et al (2016) EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 75(4):644–651
Egeli BH, Ugurlu S. Familial Mediterranean Fever: Clinical State Of The Art. QJM. 2020 Oct 20:hcaa291.
Wilson SP, Cassel SL (2010) Inflammasome-mediated autoinflammatory disorders. Postgrad Med 122(5):125–133
Touitou I (2001) The spectrum of Familial Mediterranean Fever (FMF) mutations. Eur J Hum Genet 9(7):473–483
Ben-Chetrit E, Levy M (1998) Familial Mediterranean fever. Lancet (London, England) 351(9103):659–664
Federici S, Sormani MP, Ozen S, Lachmann HJ, Amaryan G, Woo P, et al. Paediatric Rheumatology International Trials Organisation (PRINTO) and Eurofever Project. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers. Ann Rheum Dis. 2015;74(5):799–805.
Sayarlioglu M, Cefle A, Inanc M, Kamali S, Dalkilic E, Gul A et al (2005) Characteristics of patients with adult-onset familial Mediterranean fever in Turkey: analysis of 401 cases. Int J Clin Pract 59(2):202–205
Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T et al (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40(10):1879–1885
Endo Y, Koga T, Ishida M, Fujita Y, Tsuji S, Takatani A et al (2018) Musculoskeletal manifestations occur predominantly in patients with later-onset familial Mediterranean fever: data from a multicenter, prospective national cohort study in Japan. Arthritis Res Ther 20(1):257
Kishida D, Yazaki M, Nakamura A, Tsuchiya-Suzuki A, Shimojima Y, Sekijima Y. Late-onset familial Mediterranean fever in Japan. Mod Rheumatol. 2019:1–4
Ureten K, Gönülalan G, Akbal E, Güneş F, Akyürek O, Ozbek M, Oztürk MA (2010) Demographic, clinical and mutational characteristics of Turkish familial Mediterranean fever patients: results of a single center in Central Anatolia. Rheumatol Int 30(7):911–915
Tamir N, Langevitz P, Zemer D, Pras E, Shinar Y, Padeh S et al (1999) Late-onset familial Mediterranean fever (FMF): a subset with distinct clinical, demographic, and molecular genetic characteristics. Am J Med Genet 87(1):30–35
Kriegshäuser G, Enko D, Hayrapetyan H, Atoyan S, Oberkanins C, Sarkisian T (2018) Clinical and genetic heterogeneity in a large cohort of Armenian patients with late-onset familial Mediterranean fever. Genet Med 20(12):1583–1588
Kasifoglu T, Bilge SY, Sari I, Solmaz D, Senel S, Emmungil H et al (2014) Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study. Rheumatology (Oxford) 53(4):741–745
Yasar Bilge NS, Sari I, Solmaz D, Senel S, Emmungil H, Kilic L et al (2018) Comparison of early versus late onset familial Mediterranean fever. Int J Rheum Dis 21(4):880–884
Tirosh I, Yacobi Y, Vivante A, Barel O, Ben-Moshe Y, Erez Granat O, et al. Clinical significance of E148Q heterozygous variant in paediatric Familial Mediterranean Fever. Rheumatology (Oxford). 2021 Feb 9:keab128.
Atoyan S, Hayrapetyan H, Yeghiazaryan A, Ben-Chetrit E, Sarkisian T (2020) Is the country of living important in the phenotypic expression of E148Q mutation? The Armenian experience. Clin Exp Rheumatol 38(Suppl 127):124–125
Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, et al. Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005;84(1):1–11.
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Aydin, O., Egeli, B.H., Ozdogan, H. et al. Late-onset familial mediterranean fever: single-center experience and literature review. Intern Emerg Med 17, 1301–1306 (2022). https://doi.org/10.1007/s11739-021-02912-8
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DOI: https://doi.org/10.1007/s11739-021-02912-8